KLF5与c-Jun相互作用促进Ang Ⅱ诱导的血管平滑肌细胞增殖

Interaction between KLF5 and c-Jun Promotes Ang Ⅱ-induced VSMC Proliferation

KLF5(Krüppel-like factor 5)是KLF家族转录因子中的成员,参与多种与增殖相关基因的转录调节.通过体外培养大鼠血管平滑肌细胞(vascular smooth muscle cells,VSMC),以AngⅡ为增殖诱导因素,研究KLF5介导VSMC增殖的机制.研究发现,AngⅡ可剂量依赖性诱导VSMC增殖,并伴有KLF5和c-Jun蛋白表达水平的升高.为了证实KLF5参与AngⅡ诱导的细胞增殖过程,用siRNA敲低内源性KLF5的表达后,发现细胞增殖活力受到明显的抑制;交互免疫沉淀和GST pulldown分析结果显示,KLF5与c-Jun在体内和体外存在物理学上的相互作用,并且AngⅡ可诱导二者之间的相互缔合.这些结果表明,KLF5通过与c-Jun相互作用进而介导AngⅡ诱导的VSMC增殖.

Krüppel-like factor 5（KLF5） is a member of the Sp/KLF family of zinc finger factors.KLF5 is a key transcriptional factor of cardiovascular remodeling.In this study,we investigated whether KLF5 was involved in Ang Ⅱ-induced proliferation in vascular smooth muscle cells（VSMCs）.The MTT assays showed that Ang Ⅱ treatments led to an increase of VSMCs proliferation.Western blotting and RT-PCR showed that Ang Ⅱ dose-dependently induced the expression of KLF5 and c-Jun at both protein and mRNA levels.Knock-down of endogenous KLF5 expression with KLF5-specific small interfering RNA（siRNA） abrogated the induction of Ang Ⅱ on VSMC proliferation.The interaction between KLF5 and c-Jun was subsequently verified by cross-coimmunoprecipitation and GST pull-down assays.Ang Ⅱ stimulation enhanced the association of KLF5 with c-Jun.These findings suggested that KLF5 plays an important role in Ang Ⅱ-induced proliferation by interacting with c-Jun in VSMCs.